Klucel HPC - Ashland Inc....compared to wet granulation - Widest pharmaceutical and food regulatory...

Advantages of hot-melt extrusion (HME) over other processes include continuous processing efficiencies (high throughput, low cost, no solvents or water required), improved product uniformity, and enhanced solubility due to molecular dispersion of the active. HME can be used to make granules that are then tabletted or alternative dosage forms such as thin films (Figures 1 and 2).

In this application, molten thermoplastic polymers function as thermal binders during extrusion and upon cooling and solidification. Since most drugs are thermally sensitive, it is critical that the polymer can be processed at a relatively low temperature.

Klucel hydroxypropylcellulose (HPC) is the premier thermoplastic polymer for hot melt extrusion applications. This family of products is fully approved for pharmaceutical and food use and can be processed without plasticizers at significantly lower temperatures than other polymers (Table 1).

Low molecular weight grades such as Klucel EF and ELF can be used to enhance the solubility of low-soluble, Class II drugs. Klucel acts as a matrix in which drug molecules are immobilized and dispersed in a nanocrystralline or amorphous state.

Higher molecular weight grades (Klucel MF) can be used to make controlled-release tablets that are smaller, stronger, and less porous compared to those prepared via wet granulation. This allows a gel layer to be formed, retarding the dissolution of highly soluble drugs like Metformin (Figure 3).

Features and Benefits:

- Increased formulation stability – nonionic polymer that does not require plasticizer

- Low temperature processing - Enhanced solubility of low soluble actives - High molecular weight grades for sustained release

of highly soluble drugs - Stronger, smaller, and less porous tablets

compared to wet granulation - Widest pharmaceutical and food regulatory

approval compared to other thermoplastic polymers

Klucel™ HPCin hot-melt extrusion applications / controlling drug solubility in immediate- and sustained-release tablets

Table 1. Typical glass transition temperatures of polymers commonly used in hot-melt extrusion.

Polymer Tg*PVP 165ºC

Methylcellulose 150ºC

HPMC (USP 2910 Type) 140ºC

HPMCAS 120ºC

EC 120ºC

Copovidone (PVA-PVP) 115ºC

Methacrylic acid copolymer (E-type)

125-160ºC50ºC

HPC 0ºCPEO -30ºC

Figure 1. Extruded strands of nifedipine, Klucel and MCC which have been milled and compressed into tablets.

Figure 2. Extruded orange oil films using a flat die which have been cut into various shapes.

1

Converting Extruded Material to Tablets

Extruded Strands Milling Tableting

2

Using Hot Melt Extrusion to Make Films

Extruded Films Cutting Final Product

North America — Wilmington, DE USATel: +1 877 546 2782

Europe — Switzerland Tel: +41 52 560 55 00

India — MaharashtraTel: +91 22 61489696

Asia Pacific — Singapore Tel: +65 6775 5366

Middle East, Africa — Dubai, U.A.E.Tel: +971 4 3818515

Latin America — Mexico Tel: +52 55 52 76 6121

ashland.com/contact

® Registered trademark, Ashland or its subsidiaries, registered in various countries

™ Trademark, Ashland or its subsidiaries, registered in various countries

© 2017, Ashland / PC-10539.5

The information contained in this brochure and the various products described are intended for use only by persons having technical skill and at their own discretion and risk after they have performed necessary technical investigations, tests and evaluations of the products and their uses. Certain end uses of these products may be regulated pursuant to rules or regulations governing medical devices, drug uses, or pesticidal or antimicrobial uses. It is the end user’s responsibility to determine the applicability of such regulations to its products.

All statements, information, and data presented herein are believed to be accurate and reliable, but are not to be taken as a guarantee of fitness for a particular purpose, or representation, express or implied, for which seller assumes legal responsibility. No freedom to use any patent owned by Ashland, its subsidiaries, or its suppliers is to be inferred.

The Ashland Research Center in Wilmington, Delaware is equipped with a Leistritz ZSE 18-mm twin-screw extruder that can be used for customer trials and new product development. We also have wide-ranging capabilities for thermal property analysis.

Please contact your local sales representative or visit us at ashland.com/pharmaceutical to learn more about Klucel HPC and its benefits in hot-melt extrusion.

Table 2. Klucel HPC – affects of molecular weight on thermoplasticity, processing temperature and mechanical properties.

Figure 3. Dissolution profile of extruded and wet granulated 75% Metformin / 25% Klucel MF tablets.

Type MW Processing Temp. (°C)* Melt Viscosity Finished Product

Properties Solubility Rate

HF 1,150,000 205 HighestHighest tensile strength

Lowest modulusSlowest

MF 850,000 190

GF 370,000 176

JF 140,000 160

LF 95,000 150

EF 80,000 137

ELF 40,000 120 LowestLowest tensile strength

Highest modulusFastest

* approximate: no plasticizers or other additives

0

20

40

60

80

100

0 2 4 6 8 10 12

Dissolution Time (hours)

% M

etfo

rmin

Re

lea

sed

Wet GranulationHot Melt Extrusion